History and exam
Key diagnostic factors
common
presence of risk factors
Important risk factors for oesophageal cancer include male sex; older age; tobacco use; excessive alcohol intake; Barrett's oesophagus; GORD; hiatus hernia; family history of oesophageal or other cancer; low socioeconomic status; non-white race; high-temperature beverages and foods; drinking maté; a diet low in fresh fruits and vegetables; and the presence of hereditary cancer syndromes.
dysphagia
The most common presenting symptom of oesophageal cancer.
Dysphagia usually occurs only after there is obstruction of more than two-thirds of the lumen. Affected patients have generally progressed to locally advanced disease with at least T3 tumours and potentially nodal disease at the time of diagnosis.
odynophagia
Pain on swallowing is one of the signs of a locally advanced tumour, with possible invasion of the airway or mediastinum.
weight loss
One of the most common presenting signs. More than 50% of patients lose >5% of their body weight before admission for oesophagectomy, and 40% of patients lose >10%. Weight loss (independent of body mass index) is associated with increased operative risk, reduced quality of life, and poor survival in advanced disease.[88]
When not associated with odynophagia or dysphagia, weight loss may be missed and contribute to a late presentation.
European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines can be used to aid assessment and management of nutritional status.[115]
Other diagnostic factors
uncommon
hiccups
Phrenic nerve involvement can trigger hiccups.
postprandial/paroxysmal cough
This may indicate the presence of an oesophagotracheal or oesophagobronchial fistula resulting from local invasion by a tumour.
Risk factors
strong
male sex
Male sex is a risk factor for both oesophageal squamous cell carcinoma and oesophageal adenocarcinoma.[20][21] Approximately 70% of cases occur in men.[6][7]
Between 2016 and 2020, the age-adjusted rate of new cases of oesophageal cancer in the US was 7.1 per 100,000 in men, and 1.7 per 100,000 in women.[7]
The difference cannot be accounted for by other risk factors (e.g., gastro-oesophageal reflux disease, obesity), as these are equally divided between the sexes.[22]
older age
The risk of oesophageal cancer increases with age, with peak incidence between 80 and 84 years.[19]
tobacco use
Tobacco smoking strongly increases risk of oesophageal squamous cell carcinoma (OSCC) and moderately increases risk of oesophageal adenocarcinoma (OAC).[25]
Current smokers have a ninefold increased risk of OSCC compared with non-smokers.[26] Smoking increases the risk of OAC and oesophago-gastric junction adenocarcinoma approximately two- to threefold.[26][27]
With respect to OSCC, there appears to be a synergistic effect in the presence of alcohol consumption.[44][45]
excessive alcohol use (squamous cell carcinoma)
Relative risk (RR) for oesophageal squamous cell carcinoma is increased for heavy drinkers compared with non-drinkers and occasional drinkers (RR 4.95, 95% CI 3.86 to 6.34).[43] There appears to be a synergistic effect in the presence of tobacco smoke.[44][45]
There is little evidence of an association between drinking alcohol and oesophageal adenocarcinoma.[69][70]
Barrett's oesophagus (adenocarcinoma)
Barrett's oesophagus (metaplasia of the mucosal lining of the distal oesophagus) is caused by long-standing gastro-oesophageal reflux. It is a pre-malignant condition for the development of oesophageal adenocarcinoma (OAC).[28]
Risk of progression from Barrett’s oesophagus to OAC is correlated with the degree of dysplasia present. The annual progression rate of low-grade dysplasia to high-grade dysplasia or OAC is 4%; the annual risk of progression from high-grade dysplasia to OAC is 25%.[30]
A familial form of Barrett's oesophagus has been described, with multiple reports of familial clustering of patients with the condition. In a database analysis of patients diagnosed with Barrett's oesophagus or OAC in the Netherlands, 7% of cases were familial. These cases have a younger average age of onset of reflux symptoms and diagnosis of OAC than non-familial cases, suggesting a possible inherited predisposition to Barrett's oesophagus and/or OAC in some people.[31]
GORD (adenocarcinoma)
One population-based case-control study found that people with gastro-oesophageal reflux disease (GORD) had a sevenfold increase in risk of developing oesophageal adenocarcinoma (OAC) compared with people without GORD.[32]
More frequent, more severe, and longer-lasting symptoms were associated with a higher risk of cancer.[32]
Use of theophyllines or anticholinergic medications to relax the lower oesophageal sphincter has been associated with modestly increased risk of OAC, although the association may be confounded by the presence of concomitant asthma or chronic obstructive lung disease.[33]
hiatus hernia (adenocarcinoma)
The presence of a hiatus hernia increases risk of oesophageal adenocarcinoma twofold to sixfold, most probably by increasing gastro-oesophageal acid reflux.[25]
family history of oesophageal or other cancer (squamous cell carcinoma)
In one population-based cohort-control study, cumulative risk of oesophageal cancer to age 75 was 12.2% among first-degree relatives of oesophageal squamous cell carcinoma (OSCC) cases and 7.0% in those of controls (hazard ratio [HR] 1.91, 95% CI 1.54 to 2.37).[54]
Increased risk for OSCC has been associated with a family history of any cancer.[55]
low socioeconomic status
A large number of epidemiological studies have confirmed that the risk of oesophageal cancer is higher in populations with lower socio-economic status (SES).[25]
Various indicators of SES have been used in these studies, with most reporting an increased risk of two- to fourfold among those with lower SES compared with those who have higher SES.[25]
non-white race (squamous cell carcinoma)
high-temperature beverages and foods (squamous cell carcinoma)
drinking maté (squamous cell carcinoma)
Maté consumption is associated with an increased risk for oesophageal squamous cell carcinoma.[56][57] Polycyclic aromatic hydrocarbons and thermal injury have been implicated.[25]
Maté is an infusion of the herb Ilex paraguayensis (yerba maté). It is commonly consumed in southern Brazil, north-eastern Argentina, Uruguay, and Paraguay.[71] These areas also have the highest risks of oesophageal cancer in South America (mostly squamous cell).[72][73]
low intake of fresh fruit and vegetables
hereditary cancer syndromes
Tylosis (also known as focal non-epidermolytic palmoplantar keratoderma or Howel-Evans syndrome) is a rare autosomal dominant syndrome caused by germline mutations in the RHBDF2 gene. It is associated with an increased lifetime risk of developing oesophageal squamous cell carcinoma (OSCC), with an average age of diagnosis of 45 years. Routine screening by upper gastrointestinal endoscopy is recommended for patients and their family members starting from 20 years of age.[15]
Bloom syndrome is a rare autosomal recessive disorder caused by a mutation in the BLM gene, which codes for the DNA repair enzyme RecQL3 helicase.[65] It is associated with an increased risk of developing multiple cancers, especially lymphoma and acute myeloid leukaemia, lower and upper gastrointestinal tract neoplasias (including OSCC), skin cancers, and cancers of the genitalia and urinary tract.[65] Screening for gastro-oesophageal reflux disease (with or without endoscopy to detect early oesophageal cancer) may be considered.[15]
Fanconi anaemia (FA) is an autosomal recessive condition caused by germline mutations in any one of at least 21 genes associated with the FA pathway, which has a role in DNA repair. It presents with congenital abnormalities, progressive pancytopenia, and a predisposition to cancer (both haematological malignancies and solid organ tumours, particularly squamous cell carcinomas, including OSCC).[66] Upper gastrointestinal endoscopy may be considered as a screening strategy.[15]
weak
obesity (adenocarcinoma)
Elevated BMI is a risk factor for oesophageal adenocarcinoma (OAC), irrespective of the presence of gastro-oesophageal reflux disease.[34][35][36][37]
Case-control studies demonstrate a dose-dependent relationship between BMI and OAC.[37][38]
An inverse association between BMI and risk for oesophageal squamous cell carcinoma has been reported.[34][36][39][40]
human papillomavirus (squamous cell carcinoma)
achalasia
vitamin and mineral deficiencies (squamous cell carcinoma)
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